Musculoskeletal System

Question 1

Three Types of Muscles

Answer 1

• All muscles rely on calcium ions for contraction and all are innervated.

• Skeletal Muscle: Responsible for voluntary movement and is innervated by the Somatic Nervous System. Sarcomeres (repeating units of actin and myosin) give skeletal muscle a Striated (striped) appearance when viewed microscopically. Skeletal muscle is multinucleate, because individual muscle cells fuse into long rods during development. Skeletal muscle fibers contain Red Fibers (slow-twitch fibers that have high myoglobin content, hence red color, and many mitochondria to derive energy aerobically) and White Fibers (fast-twitch fibers that have low myoglobin contents, hence lighter color, and fewer mitochondria for rapid but easily fatiguing activity). Muscles of support and posture contain mostly red fibers, while muscles of quick movements contain mostly white fibers.
• Smooth Muscle: Responsible for involuntary movement and is controlled by the autonomic nervous system. Smooth muscle is non-striated and uninucleate, provides Tonus (constant state of low-level contraction such as in blood vessels), and exhibits Myogenic Activity (can contract without nervous system input in response to stretch or other stimuli).
• Cardiac Muscle: Responsible for involuntary movement and is controlled by the autonomic nervous system. Cardiac muscle is striated, can be uninucleate or binucleate, and exhibits Myogenic Activity (depolarization starts at SA Node, spreads to AV Node, then to Bundle of His or AV Bundle and its branches, and finally to Purkinje Fibers), Cardiac muscle cells are connected by Intercalated Discs containing many Gap Junctions, which allow ions to flow between cells for rapid and coordinated depolarization of muscle cells and efficient contraction of cardiac muscle.

Question 2

Sarcomere Structure

Answer 2

• Sarcomere (basic contractile unit of skeletal muscle) is made up of Thick Filaments (of Myosin) and Thin Filaments (of Actin, along with Troponin and Tropomyosin). Titin protein acts as a spring and anchors actin and myosin filaments together to prevent excessive stretching of muscle.

• Z-lines define ends of sarcomere.
• M-line runs down center of sarcomere; middle of the myosin filaments.
• I-band contains only thin filaments.
• H-zone contains only thick filaments.
• A-band contains the thick filaments in their entirety, including any overlap with thin filaments.

Question 3

Myocyte Structure

Answer 3

• Sarcomeres are attached end-to-end in series to form Myofibrils, which are surrounded by Sarcoplasmic Reticulum (modified endoplasmic reticulum that contains high concentration of calcium ions).
• Many myofibrils in parallel are encapsulated by a Sarcolemma (cell membrane), forming a Muscle Fiber or Myocytes (Muscle Cells). Sarcolemma can distribute action potential to all sarcomeres in a muscle using Transverse Tubules (T-tubules) that are oriented perpendicular to the myofibrils.
• Muscle fibers or myocytes in parallel make up a muscle.

Question 4

Sliding Filament Model of Muscle Contraction

Answer 4

• Depends on ATP and calcium.

• Initiation: Contraction starts at the Neuromuscular Junction, where Motor (Efferent) Neurons communicate with muscles. Acetylcholine is released at Motor End Plate (nerve terminal) into the synapse to bind to receptors on sarcolemma, causing depolarization. Each nerve terminal controls a group of myocytes; together, the motor end plate and its myocytes constitute a Motor Unit. Depolarization triggers an action potential, which spreads down the sarcolemma to the T-tubules to the sarcoplasmic reticulum, triggering Ca²⁺ release. The calcium ions bind to troponin and trigger a confirmational change in tropomyosin, exposing Myosin-Binding Sites on the thin actin filaments.
• Shortening of Sarcomere: Myosin carrying hydrolyzed ATP (ADP + Pi) binds with the myosin-binding site. The dissociation of ADP + Pi from myosin generates the powerstroke and result in the actin filaments sliding over the myosin filament, causing sarcomere contraction. Then, ATP binds to the myosin head, releasing it from actin. Hydrolysis of ATP to ADP + Pi causes recocking of the myosin head so that it is in position to initiate another cross-bridge cycle.
• Relaxation: Acetylcholine is degraded in the synapse by Acetylcholinesterase enzyme, terminating the signal at the neuromuscular junction and allowing the sarcolemma to repolarize. As the signal decays, calcium release ceases, and the sarcoplasmic reticulum takes up calcium from the sarcoplasm.

Question 5

Simple Twitch and Summation

Answer 5

• Muscle cells exhibit all-or-nothing response, because they are innervated by neurons which also use all-or-nothing phenomenon for action potentials. As a result, the strength of a response from one muscle cell cannot be changed; nerves control the overall force of muscle contraction by the number of motor units recruited to respond. For muscle cells to respond, stimuli must reach a threshold value.
• Simple Twitch: The response of a single muscle fiber to brief stimulus at or above threshold. Consists of Latent Period (time between reaching threshold and onset of contraction; during this time, action potential spreads along sarcolemma and calcium is released from SR), Contraction Period (muscle fiber achieves maximal force), and Relaxation Period (due to clearing of calcium from sarcoplasm).
• Summation and Tetanus: Frequency Summation occurs when contractions of muscle fibers (simple twitches) are combined to generate stronger and more prolonged contractions. Tetanus occurs when the contractions become so frequent that the muscle is unable to relax at all. Prolonged tetanus results in muscle fatigue.

Question 6

Muscle Fatigue

Answer 6

• Creatine Phosphate is created by transferring phosphate group from ATP to creatine during times of rest to serve as supplemental energy reserve; ADP is phosphorylated by creatine phosphate during muscle use to quickly generate ATP.
• Myoglobin binds oxygen with high affinity so that exercising muscles can use myoglobin reserves to keep aerobic metabolism going.

• When muscle use overwhelms the ability of the body to deliver oxygen, muscle fibers must switch to anaerobic metabolism and produce lactic acid, at which point the muscle begins to fatigue and experience Oxygen Debt (the difference between the amount of oxygen needed by the muscles and the actual amount present). After cessation of strenuous exercise, the body must convert all the lactic acid it has produced back into pyruvate using an amount of oxygen that is equal to the oxygen debt.

Question 7

Skeletal System

Answer 7

• Bone is derived from embryonic Mesoderm and can be subdivided into Compact Bone (dense and provides strength) and Spongy/Cancellous Bone (cavities created between trabeculae spicules hold bone marrow). Red Marrow is filled with hematopoietic stem cells, and Yellow Marrow stores fat.
• Long bones contain shafts called Diaphyses that flare to form Metaphyses and terminate in Epiphyses, which contain an Epiphyseal Plate that allows for longitudinal growth. Prior to puberty, the epiphyseal plate is filled with mitotic cells that contribute to growth; during puberty, these epiphyseal plates close and vertical growth is halted.
• Tendons attach muscles to bone, and Ligaments attach bones to each other.
• Bone Matrix is composed of organic components (collagen and proteins) and inorganic components (Hydroxyapatite crystals of calcium and phosphate).
• Bone Remodeling is accomplished by Osteoblasts (build bone) and Osteoclasts (resident macrophages that chew bone).
• Parathyroid Hormone is released by the parathyroid glands in response to low blood calcium to promote resorption of bone so as to increase calcium and phosphate concentrations in blood. PTH activates Vitamin D, which promotes bone resorption (this encourages bone to grow back stronger).
• Calcitonin is released by the parafollicular cells of the thyroid in response to high blood calcium to promote bone formation so as to lower blood calcium levels.